Molecular Anatomical Pathology

The Molecular Anatomic Division was established in the early 1990s and provides a unified NATA accredited Molecular Diagnostic Service for all public and regional hospitals and several private laboratories in Perth.  

The Molecular Pathology section provides patients and clinicians specialised DNA and RNA-based testing of tumours for purposes of accurate diagnosis, prognostication and prediction of response to tumour-specific therapies. Diagnostic modalities include the use of PCR, RT-PCR, digital PCR, capillary electrophoresis, pyrosequencing, multiplex-ligation dependent probe amplification (MLPA) including methylation specific MLPA, microsatellite instability (MSI), T- and B-cell gene rearrangements, Array Comparative Genomic Hybridisation, massively parallel sequencing and comprehensive genomic profiling.

In lymphomas the tests are used to establish cell lineage and B-cell or T-cell clonality, essential for accurate classification and treatment. Somatic mutation testing for a number of non-inherited cancers, such as EGFR testing for non-small cell lung cancer, are performed to determine response to tyrosine kinase inhibitor therapy. Similar testing for other genes is performed in the setting of metastatic malignant melanoma (BRAF and C-KIT mutations), gastrointestinal stromal tumours (C-KIT, PDGFRα) and colorectal cancers (KRAS and BRAF mutations), results of which impact on the choice of therapy. Testing for microsatellite instability in colorectal carcinomas is also performed to identify patients who may have hereditary non-polyposis colorectal carcinoma (Lynch Syndrome), which has implications for further genetic testing in families. In addition, methylation specific MLPA is used to further exclude Lynch Syndrome in colorectal and endometrial carcinomas.

The laboratory performs PCR-based chromosome translocation assays for accurate subtyping of lymphomas and diagnosis of sarcomas as deemed necessary by the lymphoma pathologist.  Array Comparative Genomic Hybridisation is used as an ancillary test for refining the diagnosis of morphologically ambiguous metastatic lesions.   MLPA is used for the prognostic stratification of uveal melanomas. Latest technology is in digital PCR, a highly sensitive and specific assay that can be used to detect variants that are present at very low levels, including in low amounts of DNA, for example circulating cell-free DNA extracted from blood samples are utilised. This assay is used to detect the EGFR T790M variant that confers resistance  to tyrosine kinase inhibitors in lung cancers; the MYD88 p.L265P variant for diagnosis of Lymphoplasmacytic Lymphoma and the C-KIT p.D816V variant which is used for diagnosis of mastocytosis.

The laboratory runs a number of massively parallel sequencing (MPS, Next Generation Sequencing (NGS)) panels, including a customised 33 gene cancer panel that covers clinically important biomarkers for diagnosis, prognostication and treatment selection for a broad range of common cancer types. This panel is highly suited to the analysis of colorectal, lung, melanoma, ovarian, GIST, glioma and breast cancers as it covers the most common variants in these cancer types. The panel also covers the MYD88 and KIT genes and TERT promoter which is part of the WHO guidelines for diagnostic and prognostic stratification of glioma.

In addition, the laboratory performs comprehensive genomic profiling using large MPS cancer panels which are able to analyse both DNA and RNA, thereby analysing single nucleotide and insertion/deletions variants, copy number variants, gene rearrangements, gene fusions and structural variants. This panel is particularly suitable for patients who have progressive disease, exhausted conventional treatment options, have rare cancer types or for alignment with clinical trials. The TST170 and TSO500 gene panels also analyse microsatellite instability (MSI) status and Tumour Mutation Burden which is predictive for immunotherapies. The Molecular Pathology laboratory has links with Genetic Services of WA, PathWest Discipline of Diagnostic Genomics and the Cytogenetics Laboratory.

 


Molecular Anatomical Pathology (AP) Community Health Program (CHHP)

The community Health and Hospital Program funded project entitled ‘Statewide Comprehensive Genomic Testing to Expedite Excellence in Treatment Of Western Australian Cancer Patients’ was commenced 1st July 2020. A total of $19M in funding will be received in Molecular AP over four years to provide an opportunity for comprehensive genomic profiling (CGP) using state of the art Next Generation Sequencing technology for all WA cancer patients.  CGP is providing biomarker information that is used to refine diagnosis, prognosis and align patients with the most suitable treatment strategy according to the profile of their own tumour. This has been particularly beneficial for patients for whom conventional treatment options have been exhausted.  Through this program we have successfully identified biomarkers that have led to new treatment strategies and enrolment in clinical trials. The molecular AP department now analyses a more diverse set of cancers than those routinely received, including rare cancers, such as sarcomas, which have less well understood molecular pathologies.

The project is overseen by an Advisory Committee consisting of eminent health professionals and other key leaders: Medical Oncologists, Prof Michael Millward, Prof Anna Nowak (SCGH), Dr Tom Ferguson (FSH), the Director of Population Health Genomics, Professor Kristin Nowak, clinical Professor Benhur Amanuel (Director of Services, AP, PathWest) and clinical Professor Dominic Spagnolo, Scientist-in-Charge, Molecular AP, Dr Cleo Robinson, Genetic Services Clinical Associate Professor Nick Pachter, Pathwest Chief Finance Officer, Mr Adrian Bautista and a highly experienced community member, Dr Susannah Morris, who provides important insights from the lay and lived-experience perspective.

The project has enabled the discipline to establish streamlined testing pathways across the major teaching hospitals, both public and private and also regional centres. The CHHP project provides support to both local and national programs for Comprehensive Genomic Profiling including Linear Clinical Trials, and has opened an opportunity for collaboration with the Garvan Institute in Sydney for the Molecular Screening and Therapeutics (MoST) program. Through the project we have now developed a rich network with researchers and clinicians across all of WA, including UWA, ECU and Curtin Universities and all of the major cancer treatment centres from both the private and public sectors, with experienced collaborating principal investigators at each site. In addition, we have strengthened our links with local clinical trials institutes such as the Linear Clinical Research for whom we are increasingly the designated testing centre to determine patient eligibility for trials.

Clinicians select and consent patients who would benefit from comprehensive genomic profiling and these referrals go through a rigorous workflow of pre-analytical review for specimen suitability and undergo massively parallel sequencing using the 523 gene panel followed by bioinformatics analysis and clinical interpretation of test results. The Molecular Tumour Board (MTB) meetings are now an established component of the CGP workflow. These meetings are attended by Pathologists, Clinicians and Scientists to discuss the profiling results of each case that has undergone comprehensive testing. At the meeting, which can be attended using a virtual platform, discussion of each case commences with a clinical summary providing the context for the test results in terms of pathological details, ECOG status, previous treatments, patient clinical history and family history of cancer. This enables the attendee clinicians to make a clinical recommendation based on the testing profile that is in the context of the patients’ current clinical situation in order to deliver the best outcome. Due to an increased demand for CGP these meetings are now held weekly.  Thorough the CHHP, as well as local and national collaborations, new treatment options are becoming available to WA cancer patients.

Last Updated: 28/02/2022